This renewal will continue studies of the ligand-induced factors that affect the formation of the responsive B-cell repertoire. Studies to date have demonstrated a heritable pattern of turnover in the emerging B-cell pool, which perturbed by ligand exposure. These induced perturbations are long-lasting, and result in oligoclonal profiles due to the generation of reglatory cell subsets, as well as changes in the stimulated B-cells themselves. This proposal will examine these induced regulatory cell populations, as well as the precise nature of changes which occur among the B-cells themselvs, as a result of neonatal priming. The helper requirements and specificity for primary versus secondary B-cells will be assessed by limiting dilution analysis of Th cells. The specificity, genetics, and mechanism of action of neonatally induced suppressors will be assessed by genetic studies using recombinant congenics, stimulation with various hapten-HA combinations, and examination of cell surface markers on the induced suppressors. Finally, the half-life properties of primary vs secondary B-cells will be examined through in vivo and adoptive transfer labeling studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI020450-04
Application #
3130132
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-07-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Allman, D M; Ferguson, S E; Cancro, M P (1992) Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat-stable antigenhi and exhibit unique signaling characteristics. J Immunol 149:2533-40
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Hilbert, D M; Cancro, M P (1988) Characterization of an inbred mouse exhibiting low responsiveness to phosphorylcholine. Antibodies from low-responder mice suggest gene conversion events within the S107VH gene family. J Immunol 140:4364-71
Raychaudhuri, S; Cancro, M P (1985) Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12. J Exp Med 161:816-31